RT Journal Article SR Electronic T1 Acute Effects of 3,4-Methylenedioxymethamphetamine Alone and in Combination with Ethanol on the Immune System in Humans JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 207 OP 215 VO 296 IS 1 A1 Pacifici, Roberta A1 Zuccaro, Piergiorgio A1 López, Candido Hernández A1 Pichini, Simona A1 Di Carlo, Simonetta A1 Farré, Magi A1 Roset, Pere Nolasc A1 Ortuño, Jordi A1 Segura, Jordi A1 Torre, Rafael de La YR 2001 UL http://jpet.aspetjournals.org/content/296/1/207.abstract AB Cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) alone and in combination with ethanol were assessed in a double blind, randomized, crossover, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interval between sessions of 1 week, in which single oral doses of MDMA (100 mg), ethanol (0.8 g/kg), the combination of both drugs, and placebo were tested. Acute MDMA administration produced a time-dependent immune dysfunction in association with serum concentrations of the drug as well as cortisol stimulation kinetics. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio due to a decrease in both the percentage and absolute number of CD4 T-helper cells and simultaneous increase in natural killer (NK) cells. Ethanol consumption produced a decrease in T-helper cells and B lymphocytes. The combination of MDMA and ethanol caused the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cytokines (transforming growth factor-β and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-γ) to Th2-type cytokines (interleukin-4 and interleukin-10). Disregulation in the production of pro- and anti-inflammatory cytokines with an unbalance toward anti-inflammatory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immunological homeostasis, if temporarily repeated, might alter the immune response with a risk for the general health status. The American Society for Pharmacology and Experimental Therapeutics